Biological study of naphthalene derivatives with antiinflammatory activities

Abstract

Abstract In this study, 18 synthetic naphthalene derivatives were tested for their inhibitory effects on the activation of neutrophils stimulated with N ‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP) or phorbol myristic acetate (PMA). Some of these compounds showed significant antiinflammatory activities. In general, esterification of 1‐naphthalene to compound 14 (2‐hydroxymethyl‐1‐naphthol diacetate; TAC) enhanced the antioxidant activity. Compound 15, N,N ‐bis(2‐hydroxy‐1‐naphthylmethyl) amine, has moderate inhibitory activity on neutrophils stimulated with fMLP as compared to Mannich bases of naphthylene derivatives. Either substitution at 1 or 2 position, except TAC, disfavored the inhibitory effects evoked by PMA stimulation. The influence of these compounds on the release of granule enzyme lysozyme‐induced by fMLP was measured. TAC had the highest potency on the inhibition of lysozyme release from rat neutrophil degranulation. The effects of TAC on ionic currents in a mouse neuroblastoma and rat glioma hybrid cell line, NG105‐18, were also investigated with the aid of the whole‐cell patch‐clamp technique. TAC caused an inhibitory effect on voltage‐dependent L‐type Ca 2+ current ( I Ca,L ) with an IC 50 value of 0.8 µM. The inhibitory effect of TAC on I Ca,L may not be caused by its inhibition of superoxide formation. Such an effect may, also in part, affect neuronal function. Drug. Dev. Res. 60:261–269, 2003. © 2003 Wiley‐Liss, Inc.